5-methyl-6-keto-perhydronaphthalene-1, 4-diol and processes of preparing the same



S-NIE'IHYL-fi-KETG ERHYBRONAPHIHALENE- 1,4-DIOL AND PRGCESSES FPREPARING THE SAME Lewis H. Sarett, Princeton, N. 3., assignor to Merck& Co., Inc., Railway, N. 5., a corporation of New Jersey No Drawing.Application October 31, 1955, 553%! N0. 544,077

' 4 Cim'ms. Cl. 260-586) This invention is concerned generally withdecahydronaphthalene compounds and with processes for preparing them.More particularly, it relates to the novel compoundS-methyl-6-keto-perhydronaphthalene-1,4-diol, and with the novel processof preparing this compound starting with-methyl-6-alkoxy-1,4,4a,5,8,8a-hexahydronaphthalene-1,4-dione.

This application is a continuation-in-part of copending applicationsSerial No. 216,109, filed March 16, 1951, now abandoned, and Serial No.310,133, filed September 17, 1952.

The new compound, 5-methyl-6-keto-perhydronaphtha- 1ene-1,4-diol, may bechemically represented as follows:

This compound possesses the BC ring system characteristic of certainmembers of the steroid group of compounds, and also possesses theangular methyl grouping at position together with the proper functionalsubstitution in ring C, characteristic of adrenal hormones, such ascortisone, Compound F and corticosterone. 5-methyl-6-keto-perhydronaphthalene-1,4-diol is capable of further elaboration to asteroid member and is of value a a starting material for the totalsynthesis of steroid hormones.

The 5 methyl 6 keto-perhydronaphthalene-1,4-diol, subject of the presentinvention, can be prepared by a novel process which is conducted asfollows: 5-methyl-6- alkoxy 1,4,4a,5,8,8a hexahydronaphthalene 1,4-dione(Compound 1 hereinbelow) is reacted with hydrogen in the presence of aninert solvent and a hydrogenation catalyst to form the correspondingS-methyl-G-alkoxy- 1,2,3,4,4a,5,8,8a octahydronaphthalene-l,4-dione(Compound 2) which is then reacted with lithium aluminum hydride to formthe corresponding diol, 5-methyl-6- alkoxy 1,2,3,4,4a,5,8,8aoctahydronaphthalene-1,4-dio1 (Compound 3). The latter compound is thenreacted with a hydrolyzing agent to produce 5-methy1-6-keto'perhydronaphthalene-l,4-dio1 (Compound 4).

tates Patent 0 2,785,203 Patented Mar. 12, 1957 The reactions indicatedabove may be chemically represented as follows:

CH3 CH3 H i l H t on c on! o RO% n Hydrogen noc i c en, HC\ c /onRaneyNickel Ho 2 /CH: ('3 H (I; C H I] H: 0 H2 Compound 1 Compound 2LIA1H5/ CH2 cm i H 3H I n on rel/ e re )3 RO-C 0 CH2 H+ 0:0 0 on,

[I l I i l H20\ i\ 2 n l on 0 11 an H: on n on Compound 3 Compound 4 Inthe above formulae, R stands for an alkyl radical.

The 5 methyl-6-alkoXy-1,4,4a,5,8,8a hexahydronaphthalene-1,4-diones,employed as starting materials in our process, are new compounds whichcan be prepared by reacting the corresponding 3-alkoxy-l,3-pentadienewith benzoquinone in accordance with the Dials-Alder condensationprocedure. The 3-alkoxy-1,3-pentadienes employed in this Diels-Alderprocedure can be prepared starting with the correspondingB-alkoxy-propionaldehyde as follows: The fi-alkoxy-propionaldehyde isreacted with ethylmagnesiurn bromide to produce the corresponding1-alkoxy-3 -hydroXy-pentane which is reacted with chromic acid therebyoxidizing the hydroxy substituent to form 1-alkoXy-3-keto-pentane; thelatter compound is treated with an alkyl orthoformate in alcoholsolution containing a trace of hydrogen chloride to produce thecorresponding 1,3,3-trialkoXy-pentane which is reacted with hotpotassium disulfate to produce the desired 3-alkoxy-1,3-.

pentadiene.

We ordinarily prefer to employ, as starting materials, 5-methyl-6-alkoxy1,4,4a,5,8,8a hexahydronaphthalene- 1,4-diones wherein the alkoxysubstituent in the 6-position is derived from a lower aliphatic alcohol,such as 5- methyl-G-methoxy 1,4,4a,5,8,8a hexahydronaphthalene- 1,4dione, 5 methyl-6-ethoxy-1,4,4a,5,8,8a-l1exahydronaphthalene-1,4-dione,S-methyl-6-propoxy-1,4,4a,5,8,8ahexahydronaphthalene-l,4-dione, and thelike. The bydrogenation of said 5-methyl-6-aikoxy-l,4,4a,5,8,8ahexahydronaphtha1ene-1,4-dione is conveniently carried out by dissolvingthis compound in an inert solvent such as other, dioxane, benzene, andthe like, and then bringing the resulting solution into contact withhydrogen in the presence of a hydrogenation catalyst such as Raneynickel, platinum oxide, palladium, and the like; it is ordinarilypreferred to utilize Raney nickel as the hydrogenation catalyst. Thehydrogenation mixture is agitated, preferably at'room temperature and incontact with hydrogen at a pressure of approximately one atmosphere,until approximately one molecular equivalent of hydrogen has beenabsorbed, thereby forming the correspending5-methyl-6-alkoxy-l,2,3,4,4a,5,8,8a octahydro starting material, namelythe unsaturated linkages inside the 'quinoid nucleus. This isparticularly surprising in view of the fact that it has been previouslyfound that,

7 when the unsubstituted l,4,4a,5,8,8a-hexahydro-1,4-naphthaleue-dioneis treated with catalytic hydrogen, both double bonds are readilyreduced. With chemical reducing agents, such as zinc and acetic acid,the quinoid 7 double bond may be preferentially reduced but in thepresentseries this method is always accompanied by the undesired sidereaction of hydrolysis of the enol-ether linkage. thalene-l,4-diones,either the double bond outside the quinone ring or one of the carbonylgroups, or both, are reduced. -My discovery that, by utilizing hydrogenin the presence of Va hydrogenation catalyst, it is possible toselectively reduce the double bond in the quinoid ring of 5 methyl 6alkoxy 1,4,4a,5,8,8a hexahydronaphthalene-l,4-dione, thus makes possiblethe production of the octahydronaphthalene compound having an enol-ethergrouping at position 6 adapted for conversion into a keto grouping.

The reaction between 5-methyl-6-alkoxy-1,2,3,4,4a,5,-8,8a-octahydronaphthalene-l,4-dione and lithium aluminum hydride isconducted by adding a solution of lithium aluminum hydride in an organicsolvent such as tetrahydrofuran, ether, dioxane, and the like, to asolution of said octahydro-naphthalenedione compound in said solvent.The resulting suspension .is ordinarily stirred at approximatelyroomtemperature until the reaction is substantially complete, which usuallyrequires about one-halfhoun The reaction product is recovered from thereaction mixture by mixing said reaction mixture with water todecompose. excess reducing agent and the aqueous mixture is reacted withan organic solvent such as ether, dioxane, benzene, and the like. Theor- V ganic solvent extract is then "dried and evaporated to ing agentthereby hydrolyzing the enol-ether groupingin the 6-position of themolecule. The hydrolysis .is conveniently carried out by suspending said5.-methyl-6- alkoxy 1,2,3,4,4a,5,8,8a'- .octahydronaphthalene 1,4- diolin an aqueous acid solution, .preferablya dilute aqueous solution ofacetic acid, and stirring the resulting acidic suspension atapproximately room temperature for a period of about'ten minutes. Theaqueous solution is then evaporated in vacuo to give the desired5-methyl-6- keto-perhydronaphthalene-1,4-diol which is obtained in theform of a crystalline residue.

j The .5 methyl 6 -lketo-perhydronaphthalene -.1,4- diol, thus obtained,can be converted to the therapeuti- In the case ofdiphenyl-methyl-hexahydronaphcally active material3,1l,ZO-triketo-17a-hydroiry-2lacetoxy-n -pregnene as follows: The5-methyl-.6-.ketoperhydronaphthalene-1,4-diol is reacted withN-(3-ketobutyl)-N,N-diethyl-N-methyl-ammonium iodide in the presence ofpotassium hydroxide to produce 7-keto-4bmethyl1,2,3,4,4a,4b,5,6,7,9,16,1921 dodecahydrophenanthrene-l,4-diol; thisreaction is described in detail in copending application, Serial No.228,126 filed May 24, 1951, now Patent No. 2,617,828, issued November11, 1952. V The 7-keto-4b-methyl-l,2,3,4,4a,4b,5,6,7,9,-sC,lOa-dodecahydrophenanthrene-l,4-diol is reacted with ethylene glycolin ethylene dichloride solution and in the presence of p-toluene.sulfonic acid catalyst'thereby forming 1,4 dihydroxy 4b methyl 7ethylenedioxy 1,2,3,4,4a,4b,5,6,7,8,10,1021 dodecahydrophena. .nrene.The l,4-dihydroXy-4b-methyl-7-ethylenedioxy l,2,3,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene is reacted with'cyclohexanone and aluminumisopropoxide in benzene solution to produce the correspondnanthrene.

The 1 keto 4 -'hydroxy 4b methyl 7 ethylenedioxy1,2,3,4,4a,4b,5,6,7,8,l0,10a dodecahydrophetn'oXide-pyridine complex toform 1,4 diketo 2,4b dimethyl 7 ethylenedioxy'1,2,3,4,4a,4b,5,6,7,8,10,103;

dodecahydrophenanthrene. The l,4-diketo-2,4b-dimethyl- 7 ethylenedioxy1,2,3,4,4a,4b,5,6,7,8,10,1021 dodccahydrophenanthrenc is reacted withmethallyl iodide in a tertiary 'butyl alcohol solution of aluminumtertiary butylate, thereby forming 1,4 diketo 2- methallyl 2,4b dimethyl7 ethylenedioxy 1,2,3,4,4a,4b,5,6,7,8,10,10adodecahydrophenanthrene. Thelatter compound is reacted 'in cther-benzene solution with an alkoxyacetylene magnesium bromide to produce the corresponding 1- HlliOX-thinyl 1 hydroxy 2 methallyl 2,4t dimethyl 4 keto 7 -ethylenedioxy1,2,3,4,4a,4b,5,- 6,7,8,l0,10a-dodecahydrophenanthrene. Where it isdesired to utilize another cyclic ketal, ketal, or enol-ethersubstituent to protect the 7-keto grouping, this is intro duced in theforegoing procedure by reacting the intermediate 1,4 dihydroxy 7 -keto4b methyl 1,2,3,

4,4a,4b,5,6,7,9,10,l0a dodecahydrophenanthrene under substantiallyanhydrous conditions and in the presence of an acid catalyst, with alower alkanol such as an excess amount of methanol, ethanol, propanol,butanol, 'and the like, or an excess of another low molecular weightglycol such as propylene glycol, butylene glycol, and the like.' Ifitisdesired-to use an enol-ether as the protecting group,

the 1,4 dihydroxy 7 keto 4b methyl 1,2,3,4,4a,-4b,*5,6,7,9,10,10a-dodecahydrophenanthrene is reacted, undersubstantially anhydrous conditions in the presence of anacid catalystwith an alkyl ortho formate.

The "1 alk'oxyethinyl 1 hydroxy -2 methallyl-2,4bdimethyl keto 7 eethylenedioxy l,2,3,4,4a,4'b,5,6, 7,8,ll},llla-dodecahydrophenanthreneis' reacted with a dilute aqueous mineral acid. solution to produce thecorrespending 1 .carhoalkoxymethylene 2 methallyl-2,4bdimethyl 4 keto 7ethylenedioxy 1,2,3,4,4a,4b,5,6, 7,8,10,10adodecahydrophenanthrene; thelatter compound isreacted with an alkaline saponifying agent therebyforming 1 4 'carhoxymethylene 2 methallyl 2,4bdimethyl 4 keto 7ethylenedioxy 1,2,3,4,4a,4b,5, 6,18,10,1011 dodecahydrophenanthrene. Thel-carboxymethylene 2 methallyl 2,4b dimethyl 4 keto-7- ethylene dioxy1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene is then reactedwith an alkali metal in a lower alkanol or in liquid ammonia to produce.1 carhoxymethyl -2 methallyl .2,4b dimethyl-4-- hydroxy 7 ethylenedioxy1,2,3,4,4a,4b,5,6,7,8,1-0,10a-

dodecahydrophenanthrene. This compound is reacted with an esterifyingagent, preferably an alkyl iodide in the presence of a base and/or adiazoalkane to produce the corresponding 1 carboalkoxymethyl 2methallyl- 2,4b dimethyl 4 hydroxy 7 ethylenedioxy 1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene. This compound is reactedwith an oxidizing agent, preferably under alkaline conditions, therebyforming the corresponding 1 carboalkoxymethyl 2 methallyl 2,41)-dimethyl 4 keto 7 ethylene dioxy 1,2,3,4,4a,4b,5,6,7,8,10,IOa-dodecahydrophenanthrene. The latter compound is reactedwith osmium tetroxide to form the osrnate ester of 1 carboalkoxymethyl 2(beta, gammadihydroxyisobutyl) 2,4b dimethyl 4 keto 7 ethylenedioxy1,2,3,4,4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene, which is reactedwith an aqueous alcoholic solution of an alkali metal sulfite orbisulfite to produce the corresponding 1 carboalkoxymethyl 2 (beta,gamma-dihydroxy-isobutyl) 2,4b dimethyl 4 keto- 7 ethylenedioxy1,2,3,4,4a,4b,5,6,7,8,10,1021 dodecahydrophenanthrene; the 1carboalkoxymethyl 2 (beta, gamma-dihydroxyisobutyl) 2,4b dimethyl 4keto- 7 ethylenedioxy 1,2,3,4,4a,4b,5,6,7,8,l0,10adodecahydrophenanthrene is reacted with periodic acid to form thecorresponding 1 carboalkoxymethyl 2 acetonyl- 2,4b dimethyl 4 keto 7ethylenedioxy 1,2,3,4, 4a,4b,5,6,7,8,10,10a dodecahydrophenanthrene. Thelatter compound is reacted, under substantially anhydrous conditions,with a strong alkali thereby forming A -3- ethylenedioxy11,16,20-triketo pregnene. The A -3 ethylenedioxy 11,16,20 triketopregnene is reacted with an organic sulfonyl halide thereby forming thecorresponding sulfonate ester of A -3-ethylenedioxy-1l,20-diketo-l6-hydroxy-pregnadiene, which is reacted with hydrogen in thepresence of a hydrogenation catalyst to produce dl A 3ethylenedioxy-l1,20-diketo-pregnene. The d1 A 3 ethylenedioxy 11,20diketo pregnene is treated with dirnethyl oxalate and then with alkali tform the C-21 oxalyl acid derivative. On formation of the strychninesalts of the components of this racemic mixture the d-salt precipitatesand may be recovered by filtration. Decomposition of this strychninesalt and hydroylsis of the C-21 oxalyl acid group yields3-ethylenediOxy-l1,20-diketo-A -pregnene identical with that obtainedfrom naturally occurring materials.

Iodination under alkaline conditions of the natural isomer of the21-oxalyl acid of 3-ethylenedioxy-11,20- diketo-A -pregnene, which maybe obtained in the above described resolution procedure, yields3-ethylenedioxy- 11,20-diketo-2l-iodo-u -pregnene. By treatment of thislatter compound with potassium acetate there is obtained 3 ethylenedioxy11,20 diketo-Z1-acetoxy-A -pregnene of melting point 1935-194 C.

Reaction of the last mentioned compound with hydrogen cyanide followedby dehydration of the C-20 cyanhydrin thus formed with phosphorousoxychloride yields 3 ethylenedioxy 11 keto-ZO-cyano-Zl-acetoxy- A"-pregnadiene, which may be oxidized with potassium permanganate to 3ethylenedioxy 11,20 Cllk6tO-l7ahydroxy 21 acetoxy A pregnene.3,11,20-t1iketo- 17a hydroxy 21 acetoxy A pregnene, alternatively knownas cortisone acetate, may be prepared by acid hydrolysis of the abovementioned 3-ethylenedioxy-1l,20- diketo-17a-hydroxy-2l-acetoxy-a-pregnene.

The following examples illustrate methods of carrying out the presentinvention, but it is to be understood that these examples are given forpurposes of illustration and not of limitation.

Example 1 A solution containing 510 g. (5.0 moles) ofp-ethoxypropionaldehyde dissolved in 500 cc. of ether was added, withstirring over a period of one and one-half hours, to a solution of ethylmagnesium bromide prepared from 158.2 g. (6.5 moles) of magnesium and715 g. (6.55

moles) of ethyl bromide.

while rapidly stirring the mixture and maintaining the temperature atabout 0 C. The resulting mixture was filtered and the filtered etherealsolution was evaporated in vacuo to give a liquid which was distilled invacuo to 7 give substantially pure 1-ethoxy-3-hydroxy-pentane; B. P. 55C. at 0.1 mm.

A solution containing 796 g. (8.1 moles) of concentrated sulfuric acidand 220 cc. of water was added slowly to a cold solution containing 606g. (2.0 moles) of sodium dichromate in 400 cc. of water. The resultingcold solution of chromic acid was added, over a five-hour period, to 581g. (4.4 moles) of 1-ethoxy-3-pentanol, while rapidly stirring theresulting mixture and maintaining the temperature thereof at about 10 C.During the addition of the chromic acid solution, 1500 cc. of benzenewere added to the reaction mixture to keep it fluid. Sufiicient waterwas then added to the reaction mixture to dissolve the chromium saltsand, after shaking the resulting aqueous mixture, the aqueous layer wassepa rated and set aside; the benzene layer was washed with three cc.portions of water, with one portion of an aqueous solution of a mildbase, and with one additional portion of water. The washed benzenesolution was dried over anhydrous calcium sulfate. The aqueous layer andthe three initial water washes were combined and extracted twice withpetroleum ether. The petroleum ether extracts, after two water washes,were dried, combined with the dry benzene extract, and the resultingsolution was evaporated in vacuo. The residual liquid Was purified byfractional distillation in vacuo to give substantially pure1-ethoxy-3-keto-pentane; B. P. 45 C. at 0.3 mm.'

Three cubic centimeters of 1 N ethanolic hydrogen chloride were added toa solution containing 472 g. (3.6 moles) of 1-ethoxy-3-keto-pentane, 605g. (4.1 moles) of ethyl orthoformate and 640 cc. (11 moles) of absoluteethanol. The resulting mixture was allowed to stand at room temperaturefor a period of forty hours, during which time, at scattered intervalsand in small portions, a total of twenty-four additional cubiccentimeters of 1 N ethanolic hydrogen chloride Was added to catalyze thereaction. At the end of the forty-hour reaction period, the unreactedethanol and ethyl orthoformate were evaporated from the reaction mixturein vacuo. The residual liquid was fractionally distilled in vacuo togive substantially pure 1,3,3-triethoxy-pentane; B. P. 69 C. at 1.4 mm.

A dropping funnel containing 187 g. (0.92 mole) of1,3,3-triethoxy-pentane was fitted directly onto a distilling flask inwhich was placed 0.1 g. of fused potassium bissulfate. The flasktemperature was maintained at C. for eight hours during which time the1,3,3-triethoxypentane was added dropwise onto the hot surface of thepotassium bisulfate and simultaneously dealcoholated. (At the end ofeach hour an additional 0.1 g. of potassium bisulfate was added.) Theresulting vapors were condensed and collected over an aqueous solutionof potas: sium bicarbonate. The distillate was mixed with 100 cc. ofether, the aqueous-ethanol mixture was shaken, and the ethereal layerwas separated. The ethereal solution was washed, dried over anhydrouscalcium carbonate, filtered, and the ether was evaporated from the dryethereal solution. The residual liquid was fractionally distilled togive substantially pure 3-ethoxy-l,3-pentadiene; B. P. 55 C. at 52 mm.

A mixture of 7.0 g. of 3-ethoxy-1,3-pentadiene and 4.3 g. ofbenzoquinone was shaken in a sealed flask until the mixture became warmand the quinone dissolved. The resulting solution was allowed to standat room temperature for a period of twenty hours, and the mixture wasthen cooled. The crystalline product thus formed was washed with coldpetroleum ether and the washed 7 The resulting mixture was-allowed tostand for a period of fifteen hours. At the end of this time, 1070 cc.of a saturated aqueous solution of aluminum chloride was added to theGrignard solution, 2

product was'dr ied and heated in yacuo thereby evaporatis h se r.stantially pure 5 methyl 6 ethoxy 1,4,4a ,5,8,8a-hexa- Vhydronaphthalenc -l,4-dione; M. P. 6970 C.

- Example 2' A mixture of 17, g; of 5-rnethyl-6-e'thoXyl,4,4'a,5,8,8'ahexanyd'ronfi hrneiene;1,4 aion (prepared asdescribed above and 9 g. of'Rany nickel catalyst in 200 cc'. of benzenewas treated with hydrogenuntil' one molecular equiyaleht'of h drogen hadbeen absorbed. The catalyst W'asth'en filtered on, and the solution wase l aporated to small ii'olu'rri'e and coo-led, whfeupon rosette's ofnee-lies crystallized. These were recovered by filtration and driedtoprodufceS-methyI-G-ethOXy-1,2,3,4;4'a,S;8;8a-octahydronaphthalene-lA-diOne; M.P. 118-122 C. Arzaly'sis. Calcd for Ciel-1120a: C, 70122; H, 8.17.Found: 0,7034;

Example 3 Four land eight-tenths grams ofS-methyl-fi-ethoxyl,2,3,4,4a,5,8,8aroctahydronaphthalene-1,4-dione weredissolved in 50 cc. of anhydrous tetrahydrofuran and the solution addedto a solution of 2.5 g; of lithium aluminum hydride in 100 cc. ofanhydrous .tetrahydrofuran. The resulting suspension was stirred forone-half hour, and then allowed to stand at room temperature for aperiod of twenty hours. The mixture thus obtained was poured into 1 cc.of water and the aqueous mixture was extracted with benzene. The driedbenzene solution was evaporated to dryness, leaving a crystallineresidue of 5 methyl6-ethoxy-1,2,3,4,4a,5,8,8a-octahydr0naphthalene-lA-diol; This materialwas purified by recrystallization from ether to. give substantially pure5-methyl-6- ethoxy i,2,3,4,4a,5,8.8a octahydronaphthalene-1,4-diol; M.P. ll8-122 C. A'nalysis.-Calcd for Ciel-12203: C, 68.98; H, 9.81. Found:C, 68.98; H, 9.98.

Example 4 of water was added 0.3 cc. of acetic acid. The suspension wasstirredfor ten minutes, and excess water. wasremoyed in vacuo to give a;crystalline residue or 5-riiethyl 6-li'etd perhydronaphthalene-l,4-diol;194-196 ;C. Analysisrcalcd fn pill-118035 C; 66.62; H; 9.15;- Found:C,66.-72;H,9.03. V V

Various changes and modifications may made in carrying out the presentin ention .withouit'd'eparting" from the spirit andis'cope thereof.Insofar as'the's'e changes and modifications" are within the .pur'vrew;of the annexed claims rhey'a're to be considered pan of my invention.

l'claim: v 1., The process of preparin .s-nieithyl fi-ketnaphthalene-lA-diol' which corfiprise's' rea' g" hydrogen with5-nie'thylr6-alkoxy-1;4,4a;5,8;8a hexahydronaphtha-. lene-l'A dione' inthe presence of a'hydrogenation catalyst selected from the group whichconsists of'nohle metal and nickel catalysts, thereby formin5-methyl-6-alkox 1,2,3,4,4'a,5,8;8a octahydron'aphthalene 1.4-di0ne,reacting the latter compound with lithium aluminum hydride to produce5-m'ethyl-6-alkoxy-1',2;3 ,4,4a,5,8,8a-octahydro-.

naphthalene-lA-diol, and reacting this compound with an aqueous acidicsolution. W

2. The process which. comprises reacting" hydrogen with 5-methyl6'-ethoXy- 1,4,4a,5,8,8a-heiiahydronaphtha lene-l,4-dlone,'said reactionbeing carried out by bringing the reactantstogether in benzene in thepresence of Raney nickel catalyst, thereby forming5-methyl-6-ethoxyl,2,3,4,4a,5,8,8a-octahydronaphthalehe-1,4-dione,reacting the latter compound in solution in te'trahyd'rofuran withlithium aluminum hydride to form S-n'aethyl-d} ethoxy 1,2,3',4,4a,5,8,8a octahydronaphtlialene-1,4-diol,

' and'reactiug'this.compound with anequeous acidic solution to produce5-methyl-6-ket0 perhydronaphthalene-1,4- dioll 3. The process whichcomprises reacting 5-methyl-6- alko'xy l,'2',3,4,4a,5,8,8aoetahydrbhaphthalene-l,4-diol' with an aqueous acidic solution therebyhydr'oly'zing thev enol-ether grouping in the 6-po'sition ofthe'molecule to produce 5-methyl-6-keto-perhydronaphthalene-1,4-diol.

4. S-methyl-6-keto-perhydronaphthalene-l.4-diol.

No references cited.

1. THE PROCESS OF PREPARING 5-METHYL-6-KETO-PERHYDRONAPHTHALENE-1,4-DIOL WHICH COMPRISES REACTING HYDROGEN WITH 5-METHYL-6-ALKOXY-1,4,4A,5,8,8A-HEXAHYDRONAPHTHALENE-1,4-DIONE IN THE PRESENCE OF A HYDROGENATION CATALYST SELECTED FROM THE GROUP WHICH CONSISTS OF NOBLE METAL AND NICKEL CATALYST, THEREBY FORMING 5-METHYL-6-ALKOXY1,2,3,4,4A,5,8,8A-OCTAHYDRONAPHTHALENE-1,4-DIONE, REACTING THE LATTER COMPOUND WITH LITHIUM ALUMINUM HYDRIDE TO PRODUCE 5-METHYL-6-ALKOXY-1,2,3,4,4A,5,8,8A-OCTAHYDRONAPHTHALENE-1,4-DIOL, AND REACTING THIS COMPOUND WITH AN AQUEOUS ACIDIC SOLUTION. 